Oviposition inhibitory activity of the Mexican sunflower Tithonia diversifolia (Asteraceae) polar extracts against the two-spotted spider mite Tetranychus urticae (Tetranychidae)

The Mexican sunflower (Tithonia diversifolia, Asteraceae) is an invasive shrub of agricultural and non-agricultural lands in tropical countries. Besides extensive utilizations in the traditional medicine, mainly to treat malaria, the plant is believed to have a great potential in agriculture of developing countries as a green biomass to produce fertilizer, fodder and biopesticides. The plant is known to produce tagitinins, which are sesquiterpene lactones with a bitter taste endowed with toxicity against several insects such as mosquitoes, aphids, and beetles. Here, we evaluated the potential of T. diversifolia against the two-spotted spider mite Tetranychus urticae (Tetranychidae), which is one of the most economically important arthropod pests worldwide. The leaf methanolic extract and its ethyl acetate fraction were tested for acute and chronic toxicity and for oviposition inhibitory effects. The chemical composition of the extracts was analyzed by HPLC-MSn and NMR. The main constituents were flavonoid derivatives, phenylpropanoids and sesquiterpene lactones. Among the latter, tagitinin C and tagitinin A were the major compounds. In acute toxicity assays, mortality did not exceed 50% even for the highest tested dose of 150 \u3bcg cm-3. However, in chronic toxicity assays, on day 5 from application, the methanolic extract LD50 was 41.3 \u3bcg cm-3 while LD90 was 98.7 \u3bcg cm-3. Furthermore, both T. diversifolia extracts inhibited oviposition in T. urticae. The ethyl acetate extract was the most active oviposition inhibitor, with an ED50 value of 44.3 \u3bcg cm-3 and an ED90 of 121.5 \u3bcg cm-3. Overall, the good yield rate of the extract and the high crop yield highlighted good prospects of using the extract from this plant for the development of oviposition inhibitors against mite

Cannabis sativa essential oils orally administered to CD1 mice: Tissue distribution of main constituents

The essential oil (EO) obtained from hemp (Cannabis sativa L.) biomass is rich of bioactive constituents and its oral administration can be valuable. In this paper two different hemp EOs were orally administered to CD1 mice. One EO, obtained from the fresh plant material, resulted rich in monoterpenes (monoterpene rich oil, MRO) and the other, obtained from the dried biomass, contained mainly sesquiterpenes and CBD (sesquiterpene rich oil, SRO). The blood levels of the most abundant constituents were evaluated in the animals 30 and 90 min after oral administration of hemp EOs. Furthermore, compounds were also measured in brain, liver, kidney, spleen, and cecum content to evaluate their tissue distribution at the same times. Results showed the easy absorption and the ability of the major hemp EOs constituents to reach brain, liver, and kidney. Oral administration of MRO resulted in blood levels of monoterpenes in the range 45-115 ng/g at 30 min and significant tissue distribution with the detection of monoterpenes in brain, liver, and kidney. Oral administration of SRO resulted in blood levels, at 30 min, in the range 70-80 ng/g of sesquiterpenes and 139 ng/g of CBD. The compounds are still detectable in blood and brain 90 min after oral administration and significant concentrations of terpenoids are observed in liver and kidney. MRO and SRO can be considered as valuable sources of these bioactive compounds and further investigations are needed to evaluate the potential uses of hemp EO as constituent of innovative drug formulations

Editorial for Special Issue "Antiprotozoal Activity of Natural Products"

Neglected tropical diseases (NTDs), a group of diverse infectious diseases, repre-sent the leading cause of morbidity and mortality among the world's low-income pop-ulations. These diseases are often referred to as "neglected" due to their historical lack of attention from the global health agenda and research investment, with the excep-tion of some important support from the Bill & Melinda Gates Foundation. According to the World Health Organization (WHO), over 1.5 billion people are affected by at least one NTD, causing around 500,000 deaths yearly, social discrimination, and phys-ical suffering. Although NTDs can be found worldwide, they are most prevalent in tropical areas, where factors such as limited access to clean water, favorable environ-mental conditions, and inadequate sanitation expedite their transmission. Among a core group of 20 NTDs and conditions, the infections caused by single-celled protozoan parasites, such as Human African Trypanosomiasis (sleeping sickness or HAT), Chagas disease, Leishmaniasis, and Malaria, are regarded as therapeutically challenging be-cause of their elevated fatality rates and limited treatment options. Even though Malaria is not included in the NTDs’ list, it remains a significant public health issue in many NTD-endemic regions, and it is frequently considered within the framework of initiatives aimed at managing and eradicating NTDs

Population development and landscape preference of reintroduced wild ungulates: successful rewilding in Southern Italy

Background: In the past decades, the abandonment of traditional land use practices has determined landscape changes inducing reforestation dynamics. This phenomenon can be contrasted with rewilding practices, i.e., the reintroduction of animals that may promote the recovery of landscape diversity. In this study, we explore the dynamics of expansion of two reintroduced populations of wild ungulates, Italian roe deer (Capreolus capreolus italicus) and red deer (Cervus elaphus), assessing their contribution in the recovery of landscape diversity. Methods: By using direct and indirect information on the two species, collected by nocturnal and diurnal surveys and camera trapping, we modelled a habitat suitability map, and estimated the density and distribution of the populations. We also performed a land use changes analysis, combining the presence of wild ungulates and livestock. Results and discussion: We demonstrated that deer dispersed gradually from their release location, increasing in population size, and this occurred in the entire study area. Moreover, we show that areas with lower grazing density are significantly affected by forest encroachment. A possible interpretation of this result could be that wild grazers (roe deer and red deer) prefer semi-open areas surrounded by the forest. This, in association with other factors, such as domestic grazing, could be one of the main responsible in maintaining landscape mosaic typical of the Apennine mountain, confirming the value of grazers as a landscape management tool. Moreover, we show the possibility to conserve through reintroduction the vulnerable C.c. italicus

BRCA2 Germline Mutations Identify Gastric Cancers Responsive to PARP Inhibitors

Mutations; Gastric cancers; PARP inhibitorsMutacions; Càncers gàstrics; Inhibidors de PARPMutaciones; Cánceres gástricos; Inhibidores de PARPDespite negative results of clinical trials conducted on the overall population of patients with gastric cancer, PARP inhibitor (PARPi) therapeutic strategy still might represent a window of opportunity for a subpopulation of patients with gastric cancer. An estimated 7% to 12% of gastric cancers exhibit a mutational signature associated with homologous recombination (HR) failure, suggesting that these patients could potentially benefit from PARPis. To analyze responsiveness of gastric cancer to PARPi, we exploited a gastroesophageal adenocarcinoma (GEA) platform of patient-derived xenografts (PDX) and PDX-derived primary cells and selected 10 PDXs with loss-of-function mutations in HR pathway genes. Cell viability assays and preclinical trials showed that olaparib treatment was effective in PDXs harboring BRCA2 germline mutations and somatic inactivation of the second allele. Olaparib responsive tumors were sensitive to oxaliplatin as well. Evaluation of HR deficiency (HRD) and mutational signatures efficiently stratified responder and nonresponder PDXs. A retrospective analysis on 57 patients with GEA showed that BRCA2 inactivating variants were associated with longer progression-free survival upon platinum-based regimens. Five of 7 patients with BRCA2 germline mutations carried the p.K3326* variant, classified as “benign.” However, familial history of cancer, the absence of RAD51 foci in tumor cells, and a high HRD score suggest a deleterious effect of this mutation in gastric cancer. In conclusion, PARPis could represent an effective therapeutic option for BRCA2-mutated and/or high HRD score patients with GEA, including patients with familial intestinal gastric cancer.This work was funded by the Italian Association for Cancer Research (AIRC), IG 20210 and IG 27531 to S. Giordano; IG 23624 to F. Pietrantonio; IG 21770 to S. Corso. FPRC 5×1000 2015 Min. Salute “Strategy” to SG; Fondazione Piemontese per la Ricerca sul Cancro (FPRC) 5×1000 MS2017 PTCRC-intra 2020 to S. Giordano; Ricerca Locale Dept. Oncology 2021 to S. Corso; Italian Ministry of Health-Ricerca Corrente 2022–23. B. Pellegrino was supported by ESMO with a Clinical Translational Fellowship aid supported by Roche and received research grants from GOIRC. Fondazione CR Firenze to M. Benelli

Structure/activity virtual screening and in vitro testing of small molecule inhibitors of 8-hydroxy-5-deazaflavin:NADPH oxidoreductase from gut methanogenic bacteria

Abstract Virtual screening techniques and in vitro binding/inhibitory assays were used to search within a set of more than 8,000 naturally occurring small ligands for candidate inhibitors of 8-hydroxy-5-deazaflavin:NADPH oxidoreductase (FNO) from Methanobrevibacter smithii, the enzyme that catalyses the bidirectional electron transfer between NADP+ and F420H2 during the intestinal production of CH4 from CO2. In silico screening using molecular docking classified the ligand-enzyme complexes in the range between − 4.9 and − 10.5 kcal/mol. Molecular flexibility, the number of H-bond acceptors and donors, the extent of hydrophobic interactions, and the exposure to the solvent were the major discriminants in determining the affinity of the ligands for FNO. In vitro studies on a group of these ligands selected from the most populated/representative clusters provided quantitative kinetic, equilibrium, and structural information on ligands' behaviour, in optimal agreement with the predictive computational results

Quaternary Ammonium Leucine-Based Surfactants: The Effect of a Benzyl Group on Physicochemical Properties and Antimicrobial Activity

Quaternary ammonium amphiphiles are a class of compounds with a wide range of commercial and industrial uses. In the pharmaceutical field, the most common quaternary ammonium surfactant is benzalkonium chloride (BAC), which is employed as a preservative in several topical formulations for ocular, skin, or nasal application. Despite the broad antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as fungi and small enveloped viruses, safety concerns regarding its irritant and cytotoxic effect on epithelial cells still remain. In this work, quaternary ammonium derivatives of leucine esters (C10, C12 and C14) were synthesised as BAC analogues. These cationic surfactants were characterised in terms of critical micelle concentration (CMC, by tensiometry), cytotoxicity (MTS and LDH assays on the Caco-2 and Calu-3 cell lines) and antimicrobial activity on the bacterial species Staphylococcus aureus and Enterococcus faecalis among the Gram-positives, Escherichia coli and Pseudomonas aeruginosa among the Gram-negatives and the yeast Candida albicans. They showed satisfactory surface-active properties, and a cytotoxic effect that was dependent on the length of the hydrophobic chain. Lower minimum inhibiting concentration (MIC) values were calculated for C14-derivatives, which were comparable to those calculated for BAC toward Gram-positive bacteria and slightly higher for Gram-negative bacteria and C. albicans. Thus, the synthesised leucine-based quaternary ammonium cationic surfactants can potentially find application as promising surface-active compounds with antimicrobial activity

Aniseed, Pimpinella anisum, as a source of new agrochemicals: phytochemistry and insights on insecticide and acaricide development

Pimpinella anisum L. (Apiaceae), known around the world as aniseed, is a widely cultivated crop, native of the sub-Mediterranean area. Its essential oil (EO) is exploitable in different fields such as food and beverages, pharmaceutics, cosmetics, and nutraceuticals. Regardless of the geographic origin, the EO exhibited consistent transanethole predominancy. Among the numerous biological properties exerted by aniseed EO, its antimicrobial, antifungal, insecticidal, and acaricidal effects have been extensively investigated for the formulation of biopesticides against larvae and adults of various pests and vectors. Hereafter, the published data on the insecticidal and acaricidal activity of aniseed EO and its major compounds on agricultural pests, stored-product pests, and arthropods of medical and veterinary interest is reviewed. For each study, the arthropod and the developmental stage on which the aniseed EO or the aniseed EO-based formulation were tested, the mode of action, the main constituents, and the exerted mortality, as well as the toxicity to non-target organisms and the possible sub-lethal effects are reported. The advantages of the possible use of aniseed EO as a biopesticide are analysed, as well as the current weaknesses and the critical points to be overcome to open the doors to the industrial utilization of Apiaceae EOs by the agrochemical industry

Quaternary ammonium surfactants derived from leucine and methionine: novel challenging surface active molecules with antimicrobial activity

Surfactants are versatile excipients, which are commonly employed in several pharmaceutical formulations as emulsifiers, stabilizing or solubilizing agents. In this field, current research is aimed at the design or discovery of amphiphilic molecules with improved characteristics in terms of safety (toxicological profile) and biological activities (e.g. antimicrobial activity, interaction with biomembranes). Quaternary ammonium surfactants derived from amino acids are one such class of compounds with significant potential for pharmaceuticals. In this work, quaternary ammonium surfactants derived from the amino acids leucine and methionine and esterified with fatty acid of different lengths (C10, C12 and C14) were synthesized. These amphiphiles were characterized in terms of critical micelle concentration (CMC) by tensiometry and conductivity measurements, cytotoxicity (MTS and LDH assay on Caco-2 and Calu-3 cell lines) and antimicrobial activity on selected Gram-positive (S. aureus and E. faecalis), Gram-negative (E. coli and P. aeruginosa) and the fungus C. albicans. The derivatives bearing C12 and C14 chains displayed CMC, EC50 (from cytotoxicity assays) and minimum inhibition concentration (MIC) values that are comparable to those of benzalkonium chloride (used as reference), especially towards Gram-positive and C. albicans. On the contrary, derivatives bearing C10 chains have higher CMC, EC50 and MIC values, highlighting the crucial role of the hydrophobic tails in determining both physicochemical and biological properties. The C12-C14 synthesized derivatives may represent a promising alternative to benzalkonium chloride as surface active molecules and antimicrobial agents

Investigating the phytotoxic potential of Carlina acaulis essential oil against the weed Bidens pilosa through a physiological and metabolomic approach

Essential oils (EOs) are widely studied as possible candidates for new eco-friendly herbicides for weed management due to their phytotoxicity. In this study we tested the phytotoxic potential of the EO obtained from the roots of Carlina acaulis L. (Apiaceae) against the weed Bidens pilosa L. This EO, containing 98% of the polyacetylene carlina oxide, showed strong phytotoxic effects on the plant metabolism, such as leaf necrosis, reduction of relative water content and total leaf area, and an increase in the dry weight/fresh weight ratio, suggesting a water status alteration. The EO also damaged the photosynthetic machinery, as evidenced by the significant reduction of the effective quantum yield of photosystem II (ΦII) and the maximum quantum yield of photosystem II (Fv/Fm). In addition, the non-photochemical quenching (ΦNPQ) significantly increased after spraying with C. acaulis EO. Damage to photosystem II was further demonstrated through the reduction of manganese and calcium concentrations, possibly due to an alteration in the correct functionality of the Mn4Ca cluster of the PSII. Metabolomics analysis revealed an accumulation of branched-chain amino acids, such as isoleucine and valine, which is commonly related to osmotic alterations under drought stress situations and a general reduction in sugar content (fructose, glucose, mannose, among others), suggesting reduction of the photosynthetic efficiency too. Overall, these findings suggest C. acaulis EO as a promising natural product with phytotoxic potential against weeds that deserves further investigation